US2022288183A1PendingUtilityA1
Vaccine constructs and uses thereof against staphylococcus infections
Assignee: SOCPRA SCIENCES ET GENIES S E CPriority: Oct 21, 2016Filed: Apr 5, 2022Published: Sep 15, 2022
Est. expiryOct 21, 2036(~10.3 yrs left)· nominal 20-yr term from priority
C12N 15/85C12N 15/74A61K 39/085A61P 37/04C07K 14/31A61K 2039/522C12N 15/62A61K 2039/552A61P 31/04C07K 2319/00C07K 2319/21C12N 15/09C07K 7/08
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Abstract
There is provided a fusion construct of formula (I): X-A-linker-B-Z (I) wherein: (1) A and B are identical or different and are independently: (a) a polypeptide comprising a SACOL0029 polypeptide as set forth in any one of the sequences depicted in FIG. 24 (SEQ ID NOs: 5 and 121 to 131), a SACOL264 polypeptide (SEQ ID NO: 185), a SACOL0442 polypeptide as set forth in any one of the sequences depicted in FIG. 22D (SEQ ID NOs: 29 and 82 to 92), a SACOL0718 polypeptide (SEQ ID NO: 186), a SACOL0720 polypeptide as set forth in any one of the sequences depicted in FIGS. 23I-J (SEQ ID NOs: 11 and 109 to 120), a SACOL1353 polypeptide (SEQ ID NO: 187), a SACOL1416 polypeptide (SEQ ID NO: 188), a SACOL1611 polypeptide (SEQ ID NO: 189), a SACOL1867 polypeptide as set forth in any one of the sequences depicted in FIG. 25D (SEQ ID NOs: 152 to 164), a SACOL1912 polypeptide (SEQ ID NO: 43), a SACOL1944 polypeptide (SEQ ID NO: 190), a SACOL2144 polypeptide (SEQ ID NO: 191), a SACOL2365 polypeptide (SEQ ID NO: 192), a SACOL2385 polypeptide (SEQ ID NO: 50) or a SACOL2599 polypeptide (SEQ ID NO: 193), based on the gene nomenclature from the Staphylococcus aureus COL (SACOL) genome set forth in NCBI Reference Sequence NC_002951.2; (b) a polypeptide encoded by a gene from a same operon as a gene encoding the polypeptide of (a); (c) a polypeptide comprising an immunogenic fragment of at least 13 consecutive amino acids of (a) or (b); (d) a polypeptide comprising an amino acid sequence at least 60% identical overall to the sequence of the polypeptide of any one of (a) to (c); or (e) a polypeptide comprising an immunogenic variant comprising at least 13 consecutive amino acids of any one of (a) to (c); (2) the linker is an amino acid sequence of at least one amino acid or is absent; (3) X is absent or is an amino acid sequence of at least one amino acid; and (4) Z is absent or is an amino acid sequence of at least one amino acid. Also provided are compositions and kits comprising the fusion and uses of these fusions, compositions and kits.
Claims
exact text as granted — not AI-modified1 . A fusion construct of formula (I):
X-A-linker-B-Z (1)
wherein
(1) A and B are different and
(a) wherein A is a polypeptide comprising a SACOL0029 polypeptide as set forth in any one of SEQ ID NOs: 5 and 121 to 131, or a SACOL0442 polypeptide as set forth in any one of SEQ ID NOs: 29 and 82 to 92, and
wherein B is a SACOL0720 polypeptide as set forth in any one of SEQ ID NOs: 11 and 109 to 120, a SACOL 1867 polypeptide as set forth in any one of SEQ ID NOs: 152 to 164, or a SACOL0442 polypeptide as set forth in any one of SEO ID NOs: 29 and 82 to 92;
(b) a polypeptide comprising an immunogenic fragment of at least 13 consecutive amino acids of (a); or
(c) a polypeptide comprising an amino acid sequence at least 60% identical overall to the sequence of the polypeptide of any one of (a) or (b);
(2) the linker is an amino acid sequence of at least one amino acid or is absent;
(3) X is absent or is an amino acid sequence of at least one amino acid; and
(4) Z is absent or is an amino acid sequence of at least one amino acid.
2 . The construct of claim 1 , wherein A is a polypeptide comprising a SACOL0029 polypeptide as set forth in any one of SEQ ID NOs: 5 and 121 to 131, or a SACOL0442 polypeptide as set forth in any one of SEQ ID NOs: 29 and 82 to 92, and B is a SACOL0720 polypeptide as set forth in any one of SEQ ID NOs: 11 and 109 to 120, or a SACOL 1867 polypeptide as set forth in any one of SEQ ID NOs: 152 to 164.
3 . The construct of claim 1 , wherein A is
(a) a polypeptide comprising a SACOL0029 polypeptide as set forth in any one of SEQ ID NOs: 5 and 121 to 131; (b) a polypeptide comprising an immunogenic fragment of at least 13 consecutive amino acids of (a); or (c) a polypeptide comprising an amino acid sequence at least 60% identical overall to the sequence of the polypeptide of any one of (a) or (b); and B is
(i) a polypeptide comprising a SACOL1867 polypeptide as set forth in any one of SEQ ID NOs: 152 to 164;
(ii) a polypeptide comprising an immunogenic fragment of at least 13 consecutive amino acids of (i); or
(iii) a polypeptide comprising an amino acid sequence at least 60% identical overall to the sequence of the polypeptide of any one of (i) or (ii).
4 . The construct of claim 1 , wherein is
(a) a polypeptide comprising a SACOL0442 polypeptide as set forth in any one of SEQ ID NOs: 29 and 82 to 92; (b) a polypeptide comprising an immunogenic fragment of at least 13 consecutive amino acids of (a); or (c) a polypeptide comprising an amino acid sequence at least 60% identical overall to the sequence of the polypeptide of any one of (a) or (b); and B is (a′) a polypeptide comprising a SACOL0720 polypeptide as set forth in any one of the SEQ ID NOs: 11 and 109 to 120; (b′) a polypeptide comprising an immunogenic fragment of at least 13 consecutive amino acids of (a′); or (c′) a polypeptide comprising an amino acid sequence at least 60% identical overall to the sequence of the polypeptide of any one of (a′) or (b′).
5 . The construct of claim 22 L
wherein A is
(a) a polypeptide comprising a SACOL0029 polypeptide as set forth in any one of SEO ID NOs: 5 and 121 to 131;
(b) a polypeptide comprising an immunogenic fragment of at least 13 consecutive amino acids of (a); or (c) a polypeptide comprising an amino acid sequence at least 60% identical overall to the sequence of the polypeptide of any one of (a) or (b); and B is
(1) a polypeptide comprising a SACOL0442 polypeptide as set forth in any one of SEO ID NOs: 29 and 82 to 92;
(2) a polypeptide comprising an immunogenic fragment of at least 13 consecutive amino acids of (1) or (1); or
(3) a polypeptide comprising an amino acid sequence at least 60% identical overall to the sequence of the polypeptide of any one of (1) or (2).
6 . The construct of claim 1 , wherein the immunogenic fragment (b) comprises an amino acid sequence selected from the group consisting of
(SEQ ID NO: 34)
KDTINGKSNKSRNW[[;]]
and
(SEQ ID NO: 1)
KDGGKYTLESHKELQ.
7 . The construct of claim 6 , wherein the immunogenic fragment (c) comprises an amino acid sequence selected from the group consisting of:
(SEQ ID NO: 30)
STQNSSSVQDKQLQKVEEVPNNSEKALVKKLYDRYSKDTINGKSNKSRN
WVYSERPLNENQVRIHLEGTYTVAGRVYTPKRNITLNKEWTLKELDHII
RFAHISYGLYMGEHLPKGNIVINTKDGGKYTLESHKELQKDRENVKINT
ADIKNVTFKLVKSVNDIEQV;
(SEQ ID NO: 32)
DKQLQKVEEVPNNSEKALVKKLYDRYSKDTINGKSNKSRNWVYSERPLN
ENQVRIHLEGTYTVAGRVYTPKRNITLNKEWTLKELDHIIRFAHISYGL
YMGEHLPKGNIVINTK;
and
(SEQ ID NO: 33)
DKQLQKVEEVPNNSEKALVKKLYDRYSKDTINGKSNKSRNWVYSERPLN
ENQVRIHLEGTYTVAGRVYTPKRNITLNKEWTLKELDHIIRFAHISYGL
YMGEHLPKGNIVINTKDGGKYTLESHKELQKDRENVKINTADIKNVTFK
LVKSVNDIEQV.
8 . The construct of claim 1 , wherein the immunogenic fragment (c) comprises an amino acid sequence selected from the group consisting of:
(SEQ ID NO: 21)
QFGFDLKHKKDALA;
(SEQ ID NO: 22)
TIKDQQKANQLAS;
(SEQ ID NO: 23)
KDINKIYFMTDVDL;
and
(SEQ ID NO: 24)
DVDLGGPTFVLND.
9 . The construct of claim 1 , wherein the immunogenic fragment (c) comprises an amino acid sequence selected from the group consisting of:
(SEQ ID NO: 12)
RASLSSEIKYTAPHDVTIKDQQKANQLASELNNQKIPHFYNYKEVIHTKLYKDNLFDVKAK
EPYNVTITSDKYIPNTDLKRGQADLFVAEGSIKOLVKHKKHGKAIIGTKKHHVNIKLRKDIN
KIYFMTDVDLGGPTFVLNDKDYQEIRKYTKAKHIVSQFGFDLKHKKDALALEKAKNKVDKS
IETRSEAISSISSLTG;
(SEQ ID NO: 13)
ASLSSEIKYTAPHDVTIKDQQKANQLASELNNQKIPHFYNYKEVIHTKLYKDNLFDVKAKEP
YNVTITSDKYIPNTDLKRGQADLFVAEGSIKOLVKHKKHGKAIIGTKKHHVNIKLRKDINKIY
FMTDVDLGGPTFVLNDKDYQEIRKYTKAKHIVSQFGFDLKHKKDALALEKAKNKVDKSIET
RSEAISSISSLTG;
(SEQ ID NO: 14)
ASLSSEIKYTAPHDVTIKDQQKANQLASELNNQKIPHFYNYKEVIHTKLYKDNLFDVKAKEP
YNVTITSDKYIPNTDLKRGQADLFVAEGSIKDLVKHKKHGKAIIGTKKHHVNIKLRKDINKIY
FMTDVDLGGPTFVLNDKDYQE;
(SEQ ID NO: 15)
KDINKIYFMTDVDLGGPTFVLNDKDYQEIRKYTKAKHIVSQFGFDLKHKKDALA;
(SEQ ID NO: 17)
KDINKIYFMTDVDLGGPTFVLNDKDY;
(SEQ ID NO: 16)
KDINKIYFMTDVDLGGPTFVLNDKD;
(SEQ ID NO: 19)
KDINKIYFMTDVDLGGPTFVLND;
(SEQ ID NO: 20)
KHIVSQFGFDLKHKKDALA
and
(SEQ ID NO: 18)
SQFGFDLKHKKDALA.
10 . The construct of claim 1 , wherein the immunogenic fragment (b) comprises an amino acid sequence selected from the group consisting of:
(SEQ ID NO: 165)
PYNGWSFKDATGF;
(SEQ ID NO: 167)
AHPNGDKGNGGIYK;
(SEQ ID NO: 169)
SISDYPGDEDISVM;
(SEQ ID NO: 172)
RGPKGFNFNENVQA;
(SEQ ID NO: 175)
QFESTGTIKRIKDN;
and
(SEQ ID NO: 178)
GNSGSPVLNSNNEV.
11 . The construct of claim 10 , wherein the immunogenic fragment (c) comprises the following amino acid sequence:
(SEQ ID NO: 39)
TQVKDTNIFPYNGWSFKDATGFVIGKNTIITNKHVSKDYKVGDRITAHP
NGDKGNGGIYKIKSISDYPGDEDISVMNIEEQAVERGPKGFNFNENVQA
FNFAKDAKVDDKIKVIGYPLPAQNSFKQFESTGTIKRIKDNILNFDAYI
EPGNSGSPVLNSNNEVIGWYGGIGKIGSEYNGAVYFTPQIKDFIQKHIE
Q.
12 . The construct of claim 1 , wherein the linker comprises at least four identical or different amino acids selected from the group consisting of glycine, serine, alanine, aspartate, glutamate, and lysine.
13 . The construct of claim 1 , wherein the linker comprises (GGGGS)n (SEQ ID NO: 67), (ERKYK)n (SEQ ID NO: 61); or (EAAAK)n (SEQ ID NO: 63), wherein n=1 to 5.
14 . The construct of claim 1 , wherein the X comprises a polyhistidine of 6 to 10 amino acids.
15 . The construct of claim 1 , wherein the X is absent.
16 . The construct of claim 1 , wherein the Z is absent.
17 . An isolated nucleic acid molecule encoding the construct defined in claim 1 .
18 . A vector comprising the isolated nucleic acid defined in claim 17 .
19 . A host cell comprising the vector defined in claim 18 .
20 . The cell of claim 19 , which is a live attenuated form of Staphylococcus aureus.
21 . The cell of claim 20 , wherein the live attenuated form of Staphylococcus aureus has a stabilized small colony variant (SCV) phenotype.
22 . The cell of claim 21 , wherein the live attenuated form of Staphylococcus aureus having a stabilized SCV phenotype is a ΔhemBΔ720 S. aureus.
23 . A composition comprising:
the construct of claim 1 .
24 . (canceled)
25 . The composition of claim 23 , wherein the live attenuated form of Staphylococcus aureus has a stabilized small colony variant (SCV) phenotype.
26 . The composition of claim 23 , wherein the adjuvant comprises alum, an oil, saponin, cyclicdiguanosine-5′-monophosphate (c-di-GMP), polyphosphasine, indolicidin, pathogen-associated molecular patterns (PAMPS), liposome or a combination of at least two thereof.
27 . A method for preventing and/or treating a Staphylococcal intramammary infection (IMI) in a mammal comprising administrating to the mammal an effective amount of the construct of claim 1 .
28 . The method of claim 27 , wherein the Staphylococcal IMI is caused by one or more Staphylococcus aureus strains.
29 . The method of claim 27 , wherein the mammal is a cow.
30 . (canceled)
31 . (canceled)
32 . (canceled)
33 . (canceled)
34 . (canceled)
35 . (canceled)
36 . A kit for preventing and/or treating a Staphylococcal intramammary infection (IMI) in a mammal comprising the composition of claim 23 .Cited by (0)
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